New alpha-substituted carboxylic acid derivatives



United States Patent Claims. (11. 260-3461) This invention relates to lat-substituted carboxylic acid derivatives and their production.

This application is a divisional application of application Serial 174,684, filed February 21, 1962, now Patent No. 3,257,420.

The compounds with which the invention is concerned are the tat-substituted carboxylic acid nitriles and amides represented by the general formula wherein n is an odd number at most equal to 3,

R is a member of the group consisting of the CN and CONI-I radicals, and

R is a member of the group consisting of the furyl and tetrahydrofuryl radicals-when n denotes the number 1the vinyl and l-propenylfra'dicals. When R in general Formula I is CN, the compounds of the invention have the general formula:

The nitriles of Formula II may be prepared by reacting l-naphthyl acetonitrile or a nitrile of the general formula wherein n and R have the same meanings as in Formula I, with sodamide, so as to form the alkali metal derivative of l-naphthyl acetonitrile and the nitrile of Formula ice IV are of use as intermediates in the preparation of the tat-substituted carboxylic acids and esters described and claimed in copending application Serial 174,684, filed February 21, 1962, now Patent No. 3,257,420.

The following examples illustrate the invention.

EXAMPLE 1.Preparation of a-(I-naphthyl) fl-furylpropz'onitrile I Into a wellrdried spherical .flask are introduced 580 cc.

' of dry ether, 57 g. of 90% sodarnide (1.26 mol. of

NaNH and 196 g. (1.17 mol.) of a-l-napththylacetonitrile, whereafter the mixture is heated under reflux for one hour. The flask is cooled in an ice bath and there are added drop-by-drop 157 g. (1.34 mol.) of furfuryl chloride dissolved in 157 cc. of dry ether. After heating under reflux for 6 hours, the product is carefully poured into water and acidulated with hydrochloric acid. On distillation, there are obtained 208 g. of pale yellow viscous liquid distilling at 193l96 C./ 3 mm. Hg. Yield 71.8% (theoretical quantity 289.2 g.). After redistillation, the product has the following constants:

B.P.=194195 C./2 mm. Hg

Refractive index: n =1.6l1

HI and condensing said derivative with a halonaphthyl or a halide of the general formula The amides of Formula IV may be prepared by hy- It crytallises at ambient temperature. After two recrystallisations from a mixture of ethanol and hexane in equal volumes, there is obtained a white solid having a melting point of 46.5-48 C. (on the heating-stage microscope).

- 'Gravimetric analysis gives.Calc'ul ated: C, 82.58%; H, 5.29%; N, 5.66%. Found: C, 82.21%; C, 82.99%; N, 5.45%; H, 5.33%; H, 5.33%; N, 5.27%. EXAMPLE 2. -Pre paration of a-(I-naph'thyl) fl-tetrahydrofurylpropionitrile 41.2 g. (0.25 mol) of tetrahydrofurfurylbromide are condensed with 375g. (0.224 mol.) of pt-(l-IlflPhthYD- Yield 67% (theoretical quantity 56.4 g.).

drolysing the corresponding nitrile of Formula II with mm. Hg.

acetonitrile by the same procedure as in Example 1.

After distillation, there are obtained 37.5 g. of pale yellow viscous liquid distilling at l84187 C./ 1 mm. Hg.

After redistillation, the product has a boiling point of 154 C./ 0.4

Gravimetric analysis.Calculated: C, 81.29%; H, 6.82%; N, 5.57%. Found: C, 81.01%; C, 81.14%; H, 6.63%; H, 6.79%; N, 6.05%; N, 6.10%.

62.2 g. (0.373 mol.) of l-naphthylacetonitrile are condensed with 18.5 -g. of 90% sodamide (0.425 mol. of NaNH in 185 cc. of dry ether by the procedure of Example 2. There are added drop-by-drop 80 g. (0.439 mol.) of tetrahydrofurylpropylbromide in 80 cc. of dry ether. After distillation, there are obtained 73.3 g. of slightly turbid, very viscous, yellow liquid distilling at 192194 C./0.5 mm. Hg. Yield 60%. The redistilled product has the following constants:

B.P./0.4 mm. Hg=183 C.

Gravimetric analysis.Calcul-ated: C, 81.70%; H, 7.57%; N, 5.01%. Found: C, 81.83%; H, 7.72%; N, 5.14%.

EXAMPLE 4.Preparatin of a-(I-napththyl-A hexenoic nitrile CmHuN (M=221.28)

CH-CN 11.1 g. of 90% sodamide (0.238 mol. of NaNH 'in 110 cc. of dry ether are reacted as in Example 1 with 37.5 g. (0.224 mol.) of napththylacetonitrile and 33 g. (0.244 mol.) of crotyl bromide. There are obtained 32.5 :g. of viscous yellow liquid. Yield 65.7% (theoretical quantity 49.5 g.). After two redistillations, the product has the following constants:

B.P./0.9 mm. Hg=138 C.

Gravimetric analysis-Calculated C, 86.88%; H, 6.83%; N, 6.33%. Found: C, 86.52%; 6.97%; N, 6.69%. e

Sodium methylate may be employed as condensing agent instead of sodamide.

EXAMPLE 5.Preparatian of a-(I-napththyl)-A pentenoz'c nitrile CisHmN (M=207.25)

CH-CN 11.1 g. of 90% sodamide (0.238 mol. of NaNH in 110 cc. of dry ether are reacted as in Example 1 with 37.5 g. (0.224 mol.) of l-naphthylacetonitrile and 28 g. (0.223 mol.) of allyl bromide.

The addition of allyl bromide takes place in an ice bath, and the reaction is violent.

Distillation of the final product gives 39.5 g. of pale yellow liquid distilling at 160 C./1.5 mm. Yield 85.6% The redistilled product (which can also be referred to as a-allyl-l-naphthylacetonitrile):has the following constants: B.P./0.4 mm.130 C.

B.P./0.5 mm.132 C. Density: D 1.0520 Refractive index: n =1.603

Gravimetric analysis.Calculated: C, 86.94%; H, 6.31%; N, 6.76%. Found; C, 86.94%; C, 86.87%; H, 6.29%; H, 6.15%; N, 7.11%; N, 7.04%.

Example 6.Preparation of a-(I-naphthyI) fi-furyl-propionamide C17H15N O a (M =265.29)

4.4 g. (0.079 mol.) of caustic potash in-5 cc. of water and cc. of ethylalcohol are heated under reflux for 50 hourswith 19.5 g. (0.79 mol.) of a-(l-naphthyl). B- furyl-acetonitrile. When the reaction is complete, the ethanol is evaporated in vacuo. The cooled mixture is acidulated with hydrochloric acid. The oily productis extracted with ether. After evaporation of the ether, there remains a solid residue, which is recrystallised from ethanol. There are obtained as the first fraction 2 g. of slightly yellow crystals, and then as the second fraction 1.5 g. of slightly brown crystals (total yield 50.2%). After two further recrystallisations, the product takes the form of white crystals having a melting point of 107- 108 C. (heating-stage microscope).

Gravimetric analysis.Calculated: C, 77.00%; H, 5.70%; N, 5.28%. Found: C, 77.26%; C, 77.11%; H, 5.85%; H, 5.74%; N, 5.37%; N, 5.43%.

Example 7.-Preparati0n of a-(I-naphthyl) fi-tetrahydrofuryl-propionamide CnHnNOg (N=269.32)

Q I CHCONHz 15.5 g. (0.0617 mol.) of a-(l-naphthyl) fl-tetrahydrofuryl-propionitrile are hydrolysed in the manner described in Example 6. After the treatment and evaporation of the extraction solvent (benzene), there remain 12.5 g. (yield 75%) of a crystalline mass.

After two recrystallisations from ethyl acetate, the product has the following constants:

M.P.=153 153.5 C.

Gravimetric analysis-Calculated: C, 75.83%; H,

7.11%; N, 5.20%. Found; C, 75.62%; H, 7.14%; N,

Example 8. Preparation of a-(I-naphthyl) A -hexen0ic amide CmHnNO (M=239.30)

UT H-CONHI CH;-CH=CHCH; 22 g. (0.1 mol.) of u-(l-naphthyl)A -hexenoic nitrile are hydrolysed by the procedure described in Example 6.

6 What we claim is: boxylic acid derivative represented by the general formula 1. An a-substitutecl carboxylic acid derivative rep- RZ(OH,)H CH R resented by the general formula I RKCHflr-CH-R wherein n is an odd number at most equal to 3, R is a member of the group consisting of the CN and CONH radicals, and R is a member of the group consisting of the furyl and tetrahydrofuryl radica1swhen n denotes the number wherein 1the vinyl and l-propenyl radicals, which comn is an odd number at most equal to 3, prises condensing under reflux, for about one hour R is a member of the group consisting of the CN and the l-naphthyl acetonitrile with a member of the CONH radicals, and group consisting of a halonaphthyl and a halide of R is a member of the group consisting of the furyl and the formula R (CH -X,

tetrahydrofuryl radicals-when n denotes the number wherein n and R have the same meanings as in claim 1 1-the vinyl and l-propenyl radicals. and X is a halogen, then heating under reflux about some 2. m-(l-naphthyl)-,3-fury1propionitrile. hours, to form the desired nitrile and hydrolysing under 3. u-(l-naphthyl)-,8-tetrahydrofurylpropionitrile reflux the said nitrile, for about 50 hours, with a sub- 4. a-(l-naphthyl)-E-tetrahydrofurylvaleronitrile. stantially equimolecular quantity of an alkali in the 5. a-(1-naphthy1)-A -hexenoic nitrile. presence of a lower alkyl alcohol. 6. a-(l-naphthyD-M-pentenoic nitrile. 7 (1 na hth 1) fi fi l i id References Cited by the Examiner p y )1 y w -p p Chemical Abstracts, vol. 58, page 1435 (1963). 9. a-(l-naphthyD-M-hexenoic amide.

10. Process for the production of an lat-substituted car- NICHOLAS S. RIZZO, Primary Examiner. 

1. AN A-SUBSTITUTED CARBOXYLIC ACID DERIVATIVE REPRESENTED BY THE GENERAL FORMULA 1-(R2-(CH2)N-CH(-R)-)NAPHTHALENE WHEREIN N IS AN ODD NUMBER AT MOST EQUAL TO 3, R IS A MEMBER OF THE GROUP CONSISTING OF THE CN AND CONH2 RADICALS, AND R2 IS A MEMBER OF THE GROUP CONSISTING OF THE FURYL AND TETRAHYDROFURYL RADICALS--WHEN N DENOTES THE NUMBER 1--THE VINYL AND 1-PROPENYL RADICALS. 